Water-accessible surface area

This part of the case study was broken into two sections, the original descriptor set (2,125,127) (Hansch descriptors) and a new set of descriptors calculated in MOE (6) (MOE descriptors). The MOE Descriptors were calculated for molecules assigned Gasteiger (70) partial charges in the MMFF (46-52). The new descriptor set is constructed of three properties. The water accessible surface area (ASA) calculated using a radius of 1.4 A for a water molecule and the... 

Analysis of the Hansch descriptors illustrates that increasing the lipophilicity property for this series of compounds will increase the bioactivity in a more dramatic fashion than increasing the Tafts steric parameter. Increasing the water accessible surface area (MOE descriptor) will increase the bioactivity of the compounds. But there is more than just adding lipophilicity and water accessible surface area to the molecules to increase binding affinity. A comparison of the substituents to the bioactivities illustrates that the bulkier X and Y groups increase bioactivity in conjunction with atomic partial charge distribution of the substituents. 

The C5+, and smeta values were experimentally determined, and the ASA, vdW and logP (o/w) were determined in MOE. [7t = lipophilicity parameter o+ = Hammett constant for ben-zylic cations Esmeta = Tafts steric parameter ASA = water accessible surface area vol = van der Waals volume logP (o/w) = log of the octanol/water partition coefficient.]... 

Water accessible surface area Water accessible surface area of all hydrophobic atoms... 

Water accessible surface area of all atoms with negative partial charge Water accessible surface area of all atoms with positive partial charge Total charge of the molecule Number of rotatable single bonds Log of the octanol/water partition coefficient... 

In addition, the results of absorption studies for a series of (i-adrenoceptor blockers in vitro using Caco-2 monolayers and rat intestinal segments have been used to test new descriptors [55]. For this purpose, the authors calculated dynamic molecular surface properties considering all low-energy conformations. Molecular mechanics were used to consider the flexibility of the molecules, and the van der Waals volume (vdW) and water-accessible surface areas were also calculated (Table 4.18 and 4.19). When the dynamic polar vdW surface areas were used in regression analysis to describe cell permeability data obtained in Caco-2 cells and in rat ileum, excellent correlations were obtained (r2 = 0.99 and 0.92 respectively). 

These relationships clearly indicate that the water-accessible surface area per subunit decreases as the protein molecules aggregate to form larger particles. 

Have a higher water-accessible surface area compared with their native counterparts. 

The following abbreviations are used R2 -coefficient of determination, Ntr and Nte - number of compounds in training set and test set, Rapp -apparent permeability, Pf-cellular permeability, active trp - active transport, PWASA - polar water accessible surface area, PSA - polar surface area,... 

For the purpose of the analysis of the energetics of protein unfolding, the temperature dependence of the thermodynamical parameters of the transfer to water of various low-molecular-weight compounds has been used to estimate hydration effects, applying the group additivity method in conjunction with the determination of water-accessible surface area changes upon unfolding of proteins of... 

Courtenay, E. S., M. W. Capp, and M. T. Record. 2001. Thermodynamics of interactions of urea and guanidinium salts with protein surface Relationship between solute effects on protein processes and changes in water-accessible surface area. Protein Science. 10, 2485. 

The contribution of solvent (water) to the observed changes of the thermodynamic parameters of proteins can be assumed to be proportional to the changes in water accessible sinface area of the protein groups. The water accessible surface area can be calculated from the X-ray or... 

The water-accessible surface area of a completely unfolded polypeptide chain is given by... 

Figure 13.8 shows the relation between the hydrophobicity and the water-accessible surface area for a number of amino acids. The Gibbs energy of transfer... 

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